Neutrophils mediate blood-spinal cord barrier disruption in demyelinating neuroinflammatory diseases

Aubé, Benoit; Lévesque, Sébastien A; Paré, Alexandre; Chamma, Émilie; Kébir, Hania; Gorina Mendiz, Roser; Lécuyer, Marc-André; Alvarez, Jorge I; De Koninck, Yves; Engelhardt, Britta; Prat, Alexandre; Côté, Daniel; Lacroix, Steve (2014). Neutrophils mediate blood-spinal cord barrier disruption in demyelinating neuroinflammatory diseases. Journal of immunology, 193(5), pp. 2438-2454. American Association of Immunologists 10.4049/jimmunol.1400401

Text 2438.full.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (2MB)

Disruption of the blood-brain and blood-spinal cord barriers (BBB and BSCB, respectively) and immune cell infiltration are early pathophysiological hallmarks of multiple sclerosis (MS), its animal model experimental autoimmune encephalomyelitis (EAE), and neuromyelitis optica (NMO). However, their contribution to disease initiation and development remains unclear. In this study, we induced EAE in lys-eGFP-ki mice and performed single, nonterminal intravital imaging to investigate BSCB permeability simultaneously with the kinetics of GFP(+) myeloid cell infiltration. We observed a loss in BSCB integrity within a day of disease onset, which paralleled the infiltration of GFP(+) cells into the CNS and lasted for ∼4 d. Neutrophils accounted for a significant proportion of the circulating and CNS-infiltrating myeloid cells during the preclinical phase of EAE, and their depletion delayed the onset and reduced the severity of EAE while maintaining BSCB integrity. We also show that neutrophils collected from the blood or bone marrow of EAE mice transmigrate more efficiently than do neutrophils of naive animals in a BBB cell culture model. Moreover, using intravital videomicroscopy, we demonstrate that the IL-1R type 1 governs the firm adhesion of neutrophils to the inflamed spinal cord vasculature. Finally, immunostaining of postmortem CNS material obtained from an acutely ill multiple sclerosis patient and two neuromyelitis optica patients revealed instances of infiltrated neutrophils associated with regions of BBB or BSCB leakage. Taken together, our data provide evidence that neutrophils are involved in the initial events that take place during EAE and that they are intimately linked with the status of the BBB/BSCB.

Interest & Impact

Downloads

1 since deposited on 07 Apr 2015
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item